1. Field of the Invention
The present invention relates to a method of treatment of hypertension in a mammal, particularly a human being. This method comprises the administration of a therapeutically effective hypertension treatment amount of N-acetylserotonin (NAS) to the mammal.
2. Background
Hypertension may be defined as a condition of sustained elevated arterial blood pressure, i.e., a diastolic pressure in excess of 90 mm Hg. In the majority of cases, the patients are affected by essential hypertension, which by definition means that the underlying etiologic mechanism(s) is unknown. Regardless of the mechanism, a sustained elevation of blood pressure for a period of time has been shown to result in significant cardiovascular damage throughout the body, e.g., congestive heart failure, coronary artery disease, stroke and progressive renal failure [Veterans Administration Cooperative Study Group on Antihypertensive Agents: Effects of Treatment on Morbidity in Hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg, J.A.M.A., (1967), 202, 1028 and Veterans Administration Cooperative Study Group on Antihypertensive Agents: Effects of Treatment on Morbidity in Hypertension II.Results in patients with diastolic blood pressures averaging 90 through 114 mm Hg, J.A.M.A., (1970), 213, 1143].
The benefits of drug therapy to reduce and control blood pressure have been established [Woods, J. W., Current Therapy, ed. Conn, H. F., pp. 219-220, 1981]. Since the specific etiology is not usually known, an empirical approach to the treatment of hypertensive patients is taken. Often, the choice of treatment is based on the severity of the disease and the patient's response and compliance to initial therapy. The goal of the treatment is to reduce elevated blood pressure and maintain pressure at or near normal levels.
The effect of the pineal gland extracts on the blood pressure has been first described as without any influence in some experiments and a marked fall in blood pressure in the other experiments (Howell, 1898). This inconsistency continued to be reported by the consequent studies in the beginning of the 20th century (see for rev., Horrax, 1916). Most recently, the possible hypotensive effect of the pineal gland was suggested by the finding that surgical pinealectomy induced moderate and transient hypertension in normotensive SpragueDawley rats (Zanoboni & Zanoboni-Muciaccia, 1967; see Karppanen, 1974). This suggestion was further supported by the observation of the hypotensive effect of the selective inhibitors of monoamine oxidase A type (MAO-A) which also stimulate pineal melatonin biosynthesis (Oxenkrug et al., 1984; see for rev., Oxenkrug, 1991). Furthermore, surgical pinealectomy attenuated the hypotensive effect of clorgyline, a selective monoamine oxidase-A inhibitor (Oxenkrug et al., 1986). Some authors have suggested that hypertension in pinealectomized Wistar rats depended rather on the changed reactivity to stressful stimuli than on the pineal gland deficiency (Holmes & Sugden, 1975).
In contrast to the suggested hypotensive effect of the pineal gland observed in normotensive rats, the hyperfunction of the pineal gland was reported in the spontaneously hypertensive rats (SHR), the most recognized animal model of human essential hypertension (Finocchiaro et al., 1990; Illnerova & Albrecht, 1975; Kawashima et al. 1984). In addition, surgical or chemical pinealectomy (administration of sympathetic nerve's toxin, 6-OHDA-Reuss & Oxenkrug, 1989) prevented or attenuated the development of hypertension in SHR rats (Haeusler et al., 1972) and blocked the elevation of blood pressure in episodic hypoxia (Fletcher et al., 1992).